Quiz #2 short answer Flashcards
When you wake up in the morning and turn on the light, is dopamine release increased or
decreased? How does dopamine alter the neuronal activity in the retina? (3 marks)
Decreases, reduces gap junction communications between a class of neurons in the retina is response to an increase in light intensity.
-Happens so that the retina is not get overloaded w sensory info
-lower gap junction permeability helps retina switch from using rod to cone
Certain bacteria secrete enzymes that can digest protein or carbohydrate components of the
basal lamina.
A) Why do you suppose they do so? (1 mark)
B) What other cells of the body have evolved specialized abilities to do this? (1 mark)
C) What are the 2 main classes of enzymes they secrete? (2 marks)
A) So they can invade and infect additional tissues
B) White blood cells (macrophages)
C) Metalloproteases and serine proteases
You are interested in integrin activation and perform mutagenesis studies on integrin. You find a mutant form of integrin which you call int-act, because the int-act mutation causes the extracellular domain to exist always in an unfolded state regardless of the presence or absence
of ligand. When you determine the sequence of int-act, you find that the mutation is in the intracellular domain of integrin. Explain how this intracellular mutation could affect the conformation of the extracellular domain of integrin (hint be sure to mention talin) (3 marks)
*Inside-out signaling
Change on inside = conformational change on outside
Bidirectional communication
Ligand binding causes formation of docking site and activates signal cascade, PIP2 becomes active (phosphorylated to PIP3) - changes structure of talin - opens talin binding site so that it binds to integrin - structural change in integrin - activate on extracellular site, can bind to ECM
The basal lamina is composed of many different types of proteins, one of the most abundant
ones being laminin. Laminin contains many binding sites for various proteins.
A) name 3 of proteins for which laminin contains binding sites for (1.5 marks)
B) Why is it important for laminin to be able to bind to all of these different proteins? (1.5
marks)
A) Integrins, perlecan, dystroglycan, nidogen
B) Perlecan & dystroglycan: molecule can interact with ECM
Integrins: Molecules can interact with other cells
You are working in a lab and discover a mutant form of fibronectin that has a mutation in the
RGD domain.
A) What is the function of this domain normally? (1 mark)
B) What would be the result of having a mutation that renders the RGD domain non-functional? (2 marks)
A) facilitates cell-matrix interactions
B) matrix would not bind to the cells, when matrix cannot bind cells likely will undergo apoptosis
Sam, the undergraduate working with you in your lab, has just asked for help. You and Sam are investigating the role of the b-catenin protein at adherens junctions. Your adviser has asked you to clone the b-catenin gene by PCR. When Sam took the PCR clone you produced and sequenced it, he found a mutation that would change a conserved arginine to a methionine. When Sam ran the b-catenin protein through some web-based protein domain-finding algorithms, he found that this arginine was a conserved residue in a predicted nuclear localization signal (NLS) and thus figured it did not matter that much because the b-catenin at adherens junctions must be a cytoplasmic protein. To Sam’s dismay, your adviser was horrified at this news. Explain why a protein localized at an adherens junction might need an NLS. (4 marks)
Beta catenin has a dual role, it is not just in this cell cell junction, it is also involved in WNT signalling and in the nucleus it activates the transcription of cadherin genes (transcription factor)
You are a physician with a patient complaining of hearing loss, excessive urination and back pain.
You perform a genetic analysis and analyze and urine sample. From the genetics analysis you
discover they have a mutation in their type IV collagen gene. From the urine sample you see that
they have blood and protein in their urine. Explain how a mutation in type IV collagen could
result
A) the urine sample (2 marks)
B) the hearing loss (1 mark)
A) Mutationsin the type IV collagen gene result in an irregularly thickened basal lamina in the glomerulus of the kidney - this would allow for proteins and small amounts of blood to cross into the urine
B) Type IV collagen is an integral component of the basal lamina, it is almost always one of the strands in the trimer, defects in collagen can lead to hearing loss
Collagen chains undergo a series of post-translational modifications. Due to this fact, where in the cell must collagen molecules be translated? (1 mark) To go from pro-alpha chains to procollagen 4 processes must occur, what are they? (2 marks) Which rare amino acids are found in collagen and what is their function? (2 marks)
-imported into rough ER, transported through vesicle into golgi
-trimmed, hydroxylated, glycosylated, combines with 2 other pro-alpha chains to form procollagen, (stabalized through hydroxyl groups)
Cells needs to be able to both make the ECM and degrade it, why is that important? (2 marks)
1) enables cells to divide when embedded in the matrix
2) enables cells to travel through it
The activity of proteases that degrade the ECM components has to be tightly controlled if the
fabric of tissues is not to collapse. What are the three basic control mechanisms that facilitate this? BRIEFLY explain each mechanism (3 marks)
LOCAL ACTIVATION: Activate inactive proteases, yields active plasmin
CONFINEMENT BY CELL-SURFACE RECEPTORS: Cell-surface receptors bind to proteases confining the enzyme to where it is needed
SECRETION OF INHIBITORS: Secretes protease inhibitors
Your two friends are having an argument. Henry, who works in a lab studying signal transduction,
claims that ligand–receptor interactions are higher affinity interactions than those between two
cadherin molecules. In contrast, Oliver, who works in a lab studying the cell junctions, claims that
the interactions between two cadherin molecules must be stronger, because epithelial tissues can be extremely difficult to pull apart and anchoring junctions are joined by forces that are much stronger than the usually transient interactions of a ligand and a receptor. Who is correct and why?
*Ligand-receptor interactions vs cadherin interactions
Cadherins typically bind with low affinity
Receptors bind to their specific ligand with high affinity.
Although many weak bonds form in parallel form a strong bond (as seen with cadherins and the velcro principle), the affinity itself is higher in ligand-receptor interactions.
Cadherins must control tissue segregation to make sure tissues dont stick to one another
Integrin signalling is bidirectional. Which direction is key in white blood cell migrations? Explain how the Velcro principle works as an advantage for these WBCs. (3 marks)
There are four main type of junctions that link epithelial cells to allow them to respond as a unit. What are these 4 junctions? Briefly explain their function. Give an example of each junction (5 marks)
ANCHORING JUNCTIONS: anchor cells to each other and then anchor the cells to the ECM - desosomes
OCCLUDING JUNCTIONS:
ensure nothing leaks through the epithelial layer - tight junctions
CHANNEL-FORMING JUNCTIONS:
form channels, allow the transfer of small molecules like ions between the cells
SIGNAL-RELAYING JUNCTION:
membrane bound ligand on one cell that interacts with
the membrane bound receptor on another cell and transmits signal to both - Notch/Delta
Explain how the homophilic interactions between cadherins facilitates the formation of the
neural tube. Start when you only have ectoderm, be sure to include the changes in expression of
the various cadherins involved in the process (5 marks)
-Ectoderm has high expression of E-cadherin
-From this layer,there is infolding of ectoderm
-Changes towards higher expression of N-cadherin in those cells (down-regulate E-cadherin)
-At junction of fold: upregulation of cadherin 6B
-inward invagination can actually fuse (like binds like)
-neural tube can close & yet be seperate from cells above
-Still maintain a seperate population of cadherin 6B, can differentiate and hange cadherin expression to high levels of cadherin 7 to form neural crest cells and peripheral NS
